Category Archives: CCR5-Delta32

It was the worst of times, it was the worst of times…it was the season of darkness…it was the winter of despair. (Apologies to Charles Dickens.)

In my family history, 1348 was probably the worst year, ever, and I do mean EVER – and if you have European ancestry – it was, undoubtedly, for your family too. Why?

The Plague.

The Black Plague.

The Black Death.

The Great Plague.

The Great Pestilence.

The Great Mortality.

Bubonic Plague.

And it was probably, worse, far worse, than you know, or can even imagine.

It was one of the most devastating pandemics in human history – or at least the part of human history that we know about. Between 1348 and 1350, estimates are between 30% and 60% of all Europeans died. DNA from victims tells us that the source of the plague was indeed the Yersinia Pestis bacterium, originating in Asia and spread by rat fleas on ships. The epidemic began on the island of Sicily, spread from south to north, eventually encompassing all of Europe.

And it didn’t just happen once, it happened over and over again, beginning in the mid-1300s. It appeared again and again throughout the 1300-1700s, especially in major cities, but not as widespread and all-encompassing as the initial 1348 outbreak. By the year 1400, it’s estimated that the plague had reduced the world population from about 450 million to about 300-350 million.

According to historians, the plague was reported someplace in Europe every year between 1346 and 1671. Repeated outbreaks in some areas took high percentages of the population several times. London, for example, lost half of its population initially, then again in 1471, 10-15% of the population died, and in 1479-80 another 20%. In 1563, 1593, 1603, 1625, 1636 and 1664, London lost 20% of its population with each subsequent outbreak.

This drawing depicts the Great Plague of London in 1665, which killed up to 100,000 people.

Anyone who could afford to left London for six months or so during the worst of the plague. All cats and dogs were destroyed as a preventive measure. This allowed rats to flourish and spread the disease which was carried by their fleas. The painting shows a scene of horror. After sunset carts were driven through the streets to collect the dead. They were taken to the nearest graveyard to be buried in plague pits, as shown above. Fires burned to make smoke. Pipes of tobacco were smoked, posies of herbs worn and faces covered with masks. This was thought to be protection against contagion. London was overwhelmed with fear, terror and grief.

This scene was repeated throughout Europe. Norway lost 60% of its population between 1348-1350. Paris was stricken about every 3 years, repeatedly. There were 22 outbreaks in Venice between 1361 and 1528, and again in 1576 when one third of the population, about 50,000, people died. What do you do with 1000 dead bodies every day?

So, how bad was it, personally? Wiki gives us this information about symptoms.

Contemporary accounts of the plague are often varied or imprecise. The most commonly noted symptom was the appearance of buboes (or gavocciolos) in the groin, the neck and armpits, which oozed pus and bled when opened.

Boccaccio’s description is graphic, and I’m sparing you the photos:

“In men and women alike it first betrayed itself by the emergence of certain tumours in the groin or armpits, some of which grew as large as a common apple, others as an egg…From the two said parts of the body this deadly gavocciolo soon began to propagate and spread itself in all directions indifferently; after which the form of the malady began to change, black spots or livid making their appearance in many cases on the arm or the thigh or elsewhere, now few and large, now minute and numerous. As the gavocciolo had been and still was an infallible token of approaching death, such also were these spots on whomsoever they showed themselves. ”

Ziegler comments that the only medical detail that is questionable is the infallibility of approaching death, as if the bubo discharges, recovery is possible.

This was followed by acute fever and vomiting of blood. Most victims died two to seven days after initial infection. David Herlihy identifies another potential sign of the plague: freckle-like spots and rashes which could be caused by flea-bites.

Some accounts, like that of Louis Heyligen, a musician in Avignon who died of the plague in 1348, noted a distinct form of the disease which infected the lungs and led to respiratory problems and which is identified with pneumonic plague.

“It is said that the plague takes three forms. In the first people suffer an infection of the lungs, which leads to breathing difficulties. Whoever has this corruption or contamination to any extent cannot escape but will die within two days. Another form…in which boils erupt under the armpits,…a third form in which people of both sexes are attacked in the groin.”

What did this mean to our ancestors who survived? To begin with, people were dying so fast that they could not be afforded a proper burial. Below, the citizens of Tournai burying plague victims.

Most telling, perhaps are the testimonials of the people who survived, and wrote about what they endured – the unwilling chroniclers, as it were.

“They died by the hundreds, both day and night, and all were thrown in … ditches and covered with earth. And as soon as those ditches were filled, more were dug. And I, Agnolo di Tura … buried my five children with my own hands … And so many died that all believed it was the end of the world.”

—The Plague in Siena: An Italian Chronicle

He didn’t say that he buried 5 of his children, but that he buried “my five children.” As a parent, I can’t imagine a worse day in my worst imaginings of Hell.

“How many valiant men, how many fair ladies, breakfast with their kinfolk and the same night supped with their ancestors in the next world! The condition of the people was pitiable to behold. They sickened by the thousands daily, and died unattended and without help. Many died in the open street, others dying in their houses, made it known by the stench of their rotting bodies. Consecrated churchyards did not suffice for the burial of the vast multitude of bodies, which were heaped by the hundreds in vast trenches, like goods in a ships hold and covered with a little earth.”

—Giovanni Boccaccio

In fact, it may have been even worse than we know, and killed even higher percentages of people, especially in some locations. Geoffrey reveals that 90% of the English population may have died.

“The seventh year after it began, it came to England and first began in the towns and ports joining on the seacoasts, in Dorsetshire, where, as in other counties, it made the country quite void of inhabitants so that there were almost none left alive.

… But at length it came to Gloucester, yea even to Oxford and to London, and finally it spread over all England and so wasted the people that scarce the tenth person of any sort was left alive.”

—Geoffrey the Baker, Chronicon Angliae

Because of the massive number of deaths, mass graves were utilized, like this one in Martigues, France.

Now the good news is that archaeology digs at the sites of the mass graves, allow scientists to unquestionably identify the DNA of the culprit bacteria in different locations, across Europe, including France, Holland and England, and compare them. It appears from the genetic evidence that the plague may have come in waves, at least two different times, but the plague of the 1300s and 1400s is almost identical to that which hit Madagascar in 2013. So, the plague is not dead, just lurking, in the fleas of rats.

I wondered, how many of my ancestors died? We know that every one of my ancestors lived at least long enough to procreate, and at least one of their children lived long enough to procreate too. When you think about it, given all of the death – repeatedly – it’s nothing short of a miracle that we’re here at all. We are the offspring of the lucky ones.

How does that translate into what happened to my family members? I may not know who they were, their names, but assuredly, they lived then, were alive, functioning members of medieval society. How many were there? Assuming a 25 year generation, here’s how many ancestors we had living in the year 1350.

Generational Years

Ancestors

1950

2

1925

4

1900

8

1875

16

1850

32

1825

64

1800

128

1775

256

1750

512

1725

1,024

1700

2,048

1675

4,096

1650

8,192

1625

16,384

1600

32,768

1575

65,536

1550

131,072

1525

262,144

1500

524,288

1475

1,048,576

1450

2,097,152

1425

4,194,304

1400

8,388,608

1375

16,777,216

1350

33,554,432

If you allow for pedigree collapse, let’s say that half of these people were actually the same person, meaning that I’m descended from that person twice. That reduces the number of ancestors alive at that time to only about 16.5 million. Ok, now let’s say one third of them died, which is about 5 million. If half died, that’s about 8 million. Even if we collapse the pedigree by another 50%, which would be equivalent to a 30 year generation, 2.5 to 4 million ancestors, all dying at about the same time is a cataclysmic event in any family tree. And if you’re European and alive today, your tree suffered this same agonizing event, or series of events. The great irony is, that as horrific as this had to have been – I’ve never heard of a story, any oral history, in any family, that details or even suggests that this happened – and it was only about 650 years, or 23-25 generations, ago.

It’s a huge, huge loss, however you count it. The agony for those who remained to grieve their losses must have been immense, and intense. The very social fabric of families, communities and governments was torn from asunder the population. Blame was laid in many places, with many people, for many reasons, but never attributed to rats. And the people just kept dying.

This painting, from 1562, titled “The Triumph of Death,” by Pieter Bruegel reflects the social upheaval and terror that follow the plague that devastated Europe. The aftermath of the plague created a series of religious, social, and economic upheavals, which had profound effects on the course of European history. It took 150 years for Europe’s population to recover. No family was left untouched, and I’m sure many were simply wiped from the face of the earth.

Which brings up a question – how did my ancestors manage to survive? Was there some sort of advantage conferred upon some that others didn’t have? And if so, why?

Indeed, there may have been a protector. It’s called CCR5-delta32, where delta means deletion, and its found on chromosome 3. The receptor looks like this:

This particular deletion of a gene sequence has a specific impact on T cells and blocks the entry of disease agents. This deletion is found in between 4 and 20% of Europeans, but not in Africans or Asians. We know that it historically has protected people from smallpox, and it protects people from AIDS today. Initially it was thought that it also played a role in protecting people from the plague, but a second paper suggests otherwise. The jury is still out.

It would be interesting to determine the percentage of people who died from the plague that carried the deletion. If the percentage of plague victims with the double deletion is equal to the European percentage that carry CCR5-delta32 today, then it’s unlikely that the deletion conferred any protection, assuming the European percentage of CCR5-delta32 would have been approximately the same at that time as it is today.

If you want to know if you have the CCR5-delta32 deletion, there are two ways to find out.

You can also browse your raw data, as shown below. In this case, if you have two copies of the deletion, you’re “fully protected,” whatever “fully protected” turns out to mean. One copy means you’re partially protected, which may mean that you can become infected but the infection does not progress to full blown AIDs, or it progresses more slowly. No deletion means that you have no protection. The individual in the example below has one copy of the deletion, the other is normal.

If you ordered your 23andMe test after November 2013 and don’t have health results, you’re not entirely out of luck. You can order the test individually at Family Tree DNA, if you are already a customer, by clicking on “Order an Upgrade,” then “Order an Advanced Test,” then follow the instructions below. The test costs $39.

The CCR5 mutation is autosomal, which means, of course, that you receive a copy from each parent.

In my case, I don’t carry the deletion, so neither of my parents carried two copies of the deletion or I would have inherited the deletion.

Of my children, one does have one copy of the deletion, and the other has no copies.

So, obviously, the plague did not kill everyone who didn’t carry two copies of the mutation, or today’s European descendants would only carry the mutated (deleted) version of the gene in question.

Still, for our ancestors, and our individual European families, regardless of how, why or protection conferred, 1348 was a really, really bad year from every possible perspective. It was indeed, the season of darkness, the winter of despair.

While I can’t tell you their names, I know they died, horrible deaths, buried in mass graves – and all I can do today is to remember them namelessly – my thousands of ancestors who died in 1348.